RESUMEN
BACKGROUND Piwi-interacting RNA (piRNA) is the largest class of small non-coding RNA, which has also been identiï¬ed in somatic tissues, and aberrant expression of piRNAs in tumor tissues may be implicated in carcinogenesis. piR-823 is increased in liver cirrhosis and hepatocellular carcinoma (HCC). However, there is no report on the function of piR-823 in hepatic stellate cells (HSCs) activation during hepatic fibrosis. The present study investigated the role of piR-823 in HSC activation. MATERIAL AND METHODS Liver fibrosis was induced in mice by carbon tetrachloride (CCL4) injection and bile duct ligation (BDL). The primary HSCs were isolated from mice and cultured. The expression of piR-823 was measured by real-time PCR. The effect of piR-823 on HSCs was evaluated by either sense sequence or antisense sequence of piR-823 carried by liposome. Proteins binding to piR-823 were assayed by RNA pull-down technique and liquid chromatography-mass spectrometry (LC-MS). RESULTS Our data for the first time show that piR-823 is signiï¬cantly upregulated in activated HSCs. Overexpression of piR-823 promoted HSC proliferation, α-SMA and COL1a1 production, whereas inhibition of piR-823 suppressed the activity of HSCs. Interestingly, the combination of piR-823 and EIF3B promoted TGF-ß1 expression. CONCLUSIONS Our data illustrate a novel mechanism of piR-823 in HSC activities. The combination of piR-823 and EIF3B increased TGF-ß1 expression, which activates HSCs in liver fibrosis. piR-823 may be a new target in the treatment of liver fibrosis.
Asunto(s)
Factores Eucarióticos de Iniciación/metabolismo , Células Estrelladas Hepáticas/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Cirrosis Hepática/metabolismo , ARN Interferente Pequeño/metabolismo , Animales , Tetracloruro de Carbono , Proliferación Celular/fisiología , Factores Eucarióticos de Iniciación/genética , Células Estrelladas Hepáticas/patología , Péptidos y Proteínas de Señalización Intracelular/genética , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/patología , Masculino , Ratones , Ratones Endogámicos C57BL , MicroARNs/genética , Cultivo Primario de Células , ARN Interferente Pequeño/genética , Transducción de Señal , Activación Transcripcional , Factor de Crecimiento Transformador beta1/metabolismo , Regulación hacia ArribaAsunto(s)
Catárticos/uso terapéutico , Colon Descendente/patología , Neoplasias del Colon/patología , Lipoma/patología , Cuidados Preoperatorios , Adulto , Colon Descendente/diagnóstico por imagen , Colon Descendente/cirugía , Neoplasias del Colon/diagnóstico por imagen , Neoplasias del Colon/cirugía , Resección Endoscópica de la Mucosa , Femenino , Humanos , Lipoma/diagnóstico por imagen , Lipoma/cirugía , Rotura Espontánea/patología , Rotura Espontánea/cirugía , Tomografía Computarizada por Rayos XRESUMEN
Backgroud: Obstructive jaundice increases intestinal permeability, but the pathological mechanisms remain obscure, which results in debates about the necessity of performing preoperative biliary drainage in patients with obstructive jaundice. Mucin-2 (MUC2) and goblet cells regulated by bile acids play an important role in maintaining the function of intestinal mucosal barrier. The present study was to investigate the role of goblet cells and MUC2 in obstructive jaundice and evaluate the effect of biliary drainage on intestinal permeability. STUDY DESIGN: We enrolled patients with malignant biliary obstruction and controls. We also did animal studies with four groups of rats: sham operation, obstructive jaundice, internal biliary drainage, and external biliary drainage. Histopathological analysis, biochemical measurement, and electron microscopy examination were done on pertinent samples. RESULTS: Compared with the control group, the small intestinal mucosa was significantly damaged; goblet cells and MUC2 were significantly decreased and serum endotoxin level was significantly increased in patients and rats with obstructive jaundice. Biliary drainage, especially internal biliary drainage, significantly increased goblet cells and MUC2 and attenuated the damage of small intestinal mucosa. CONCLUSIONS: In obstructive jaundice condition, goblet cells and MUC2 were reduced which were involved in the damage of intestinal mucosa barrier; biliary drainage increased goblet cells and MUC2, repaired mucosa layer and restored the intestinal mucosa barrier function.